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Mummified child died of Hep B, not smallpox

Genetic analysis overturns diagnosis for Medieval child held to be the earliest smallpox case in Europe. Andrew Masterson reports.

A mummified Medieval child thought to have died from smallpox in fact perished because of Hepatitis B virus, genetic sequencing reveals.

The infant was interred in the Basilica of St Domenico Maggiore in Naples, Italy, during the Sixteenth Century, and has been the subject of intense scrutiny in recent decades, in part because of its noticeably lesion-covered skin.

In 1990, the World Health Authority initiated an examination of the mummy. In its subsequent report, a team led by Svetlana Marennikova of the WHO’s Smallpox Eradication Program used electron microscopy to detect “well-preserved virus-like structures” which were identified as variola, the cause of smallpox.

The study established the child as the earliest confirmed case of smallpox in Europe. Crucially, however, Marennikova’s team did not conduct DNA analysis and relied only on physical characteristics to make their findings.

That DNA analysis has now been done, and the poor lesion-covered child is no longer the flag-bearer for smallpox, but instead represents the earliest confirmed case of Hepatitis B in Europe.

A team led by evolutionary geneticist Hendrik Poinar of the McMaster Ancient DNA Centre in Canada extracted tiny fragments of skin and bone from the remains, then subjected them to advanced screening techniques to extract DNA fragments and stitch them together.

The result was a complete genome of an ancient strain of Hepatitis B virus. The lesions on the boy’s face – assumed to be symptomatic of smallpox – are now thought to be the result of a hepatitis-linked rash called Gianotti-Crosti syndrome.

In a paper published in the journal PLOS Pathogens, Poinar and colleagues note that the 450-year-old virus genome is markedly similar to its modern counterpart. Frustratingly, neither version contains suitable markers to allow researchers to deduce the virus’s mutation rate.

Nevertheless, the overturning of the initial smallpox diagnosis opens doors for further investigation into both diseases.

“The more we understand about the behaviour of past pandemics and outbreaks, the greater our understanding of how modern pathogens might work and spread, and this information will ultimately help in their control,” says Poinar.

In 2016, researchers from the McMaster Ancient DNA Centre investigated another mummified child – this time one dating from the mid-Seventeenth Century and found in the crypt of the Dominican Church of the Holy Spirit in Vilnius, Lithuania.

The child showed no visible signs of smallpox, but sequencing produced a complete variola genome. The elimination of the virus in the Naples child reinforces the researchers’ conclusion that “smallpox is a much more recent infection in humans than previously presumed”.